This research is aimed at obtaining specific information about the regulation of macromolecular synthesis in developing brain, and particularly to elucidate the role of growth promoting hormones in the central nervous system during development. It is proposed to investigate general and specific aspects of RNA and protein synthesis in neonatal rat brain, both in vivo and in vitro before and after administration of pituitary growth hormone, subprimate placental lactogen, or insulin. The effects of hormone administration on RNA and protein synthesis in rat brain will also be studied as a function of postnatal age over the time of CNS development and in specific brain parts, particularly cerebellum, where significant development occurs between birth and 21 days of age. In addition to general studies of nucleotide incorporation into RNA, investigations will be carried out to examine the effects of hormones on RNA polymerase activity, species of RNA, capping and methylation of mRNA, and mRNA synthesis is a cell free system. In addition to general investigation of the effects of hormones on the incorporation of radio-labelled amino acids into protein and the pattern of protein synthesis in neonatal rat brain, it is proposed to study the effects of the growth promoting hormones on ribosomal aggregation, initiation, aminoacylation of tRNA and elongation activity. A second major objective is to correlate the effects on RNA and protein synthesis with those previously observed on polyamine synthesis and ornithine decarboxylase activity in the developing rat brain. In addition to measurement of enzyme activity and polyamine levels, the relationships between polyamine, RNA, and protein synthesis will be studied through the use of specific inhibitors of ornithine decarboxylase activity. Finally the isolation of rat brain ornithine decarboxylase will be undertaken by affinity chromatography as well as conventional methods of protein purification in order to provide pure enzyme for development of radioimmunoassay for brain ornithine decarboxylase. This will facilitate the investigation of control of de novo synthesis of ornithine decarboxylase in response to regulatory agents.